[Cost-effectiveness study of olanzapine pamoate: Mirror-image analysis after one year]. / Étude coût-efficacité du pamoate d'olanzapine : analyse en miroir sur un an.

INTRODUCTION: Olanzapine pamoate has a higher cost of treatment than the oral form and requires administration in a hospital setting (unlike other long-acting antipsychotics), and the cost-effectiveness of this treatment may be questioned. Many scientific societies and national health systems are increasingly interested in the pharmacoeconomic impact of health products. The search for efficacy of a treatment can be done in two ways: medico-economic modeling studies or observational studies i.e. randomized controlled trials or mirror studies. The models are based on theoretical models from published clinical data simulating the course and evolution of patient health conditions, which benefit from a particular therapeutic strategy. Even if the design of observational mirror studies makes it possible to get closer to the clinical reality by observing the patient before and after the initiation of the treatment, the majority of the pharmacoeconomic studies published on olanzapine pamoate are modeling works that do not reflect actual conditions of care. The Guillaume Régnier Hospital Center in Rennes has a large cohort of patients treated with olanzapine pamoate: 121 instauration treatments are recorded from April 1, 2010 to Mars 1, 2015. The objective of this study is to evaluate the cost-effectiveness of olanzapine pamoate in actual clinical practice. METHODS: This is a one-year cost-effectiveness retrospective observational mirror-image study of a cohort of 52 patients with schizophrenia who were treated for at least three months with olanzapine pamoate. The primary efficacy endpoint is the differential in the number of full-time hospitalizations before and after the introduction of olanzapine pamoate versus the hospital cost differential. The secondary criteria are the difference of the number of the days spent in hospital and the number of outpatient consultations between the year preceding the injection and the year following it. The results were calculated on the general cohort and within 2 subgroups: patients treated for more than one year and those receiving less than one year of treatment with olanzapine pamoate. RESULTS: Fifty-two patients were included (median age=35 years, sex ratio H/F=2.7) and only 38.5% discontinued treatment. For patients who maintained long-acting treatment, they received a dosage of 25mg oral olanzapine (min=7.5mg, max=60mg), 5mg more medially than the group having stopped the olanzapine pamoate (20mg; min=10mg, max=40mg). The majority of these patients were receiving off-label authorized marketing doses of oral olanzapine, whereas 22% of them had off-label dosages of olanzapine pamoate. The main causes of discontinuation were symptom persistence, loss of vision and the occurrence of adverse effects (including weight gain and sedation). Olanzapine pamoate significantly reduced the number of hospitalizations compared to the previous management strategy (1 less hospitalization, P<0.001 in patients treated more than one year and in the general cohort). As a logical consequence the number of hospitalization days in day care increased after the establishment of this long-acting antipsychotic with hospital reserve status (18 in median; min=0, max=159). We observed a non-statistically significant tendency of decrease in the number of days of full-time hospitalization and an increase in the number of ambulatory procedures, particularly in patients who have maintained the treatment for one year. This efficiency had a non-significant additional cost of €3361 per year. There was an average multiplication by 8,5 of the drug cost a year later in the general cohort (5.5 in the group of patients treated less than one year and 10.4 in the group of patients who maintained it a year). There was a 23,2% average increase in the cost of hospitalization in the general cohort (3.75 % in patients who maintained treatment compared to 48.9% in patients who discontinued treatment). CONCLUSION: By its mirror design, the study was placed in real conditions of care of the patient with schizophrenia. A total of 61.5% of patients maintained treatment with olanzapine pamoate for a minimum of one year. This APAP is more effective without significantly increasing the cost compared to the previous therapeutic strategy (including oral olanzapine). The additional cost is partly due to the administration restriction in a hospital setting in relation to risk of Post-Injection Delirium/Sedation Syndrom (PDSS). There is currently no acceptable efficiency limit. The results of this cost-effectiveness analysis cannot be extrapolated to the other long-acting antipsychotics since it is the only one with hospital reserve status. The current limitations of medico-economics in psychiatry derive from the heterogeneity of clinical forms and the management of mental pathologies.

Stability of oral liquid preparations of methylergometrine.

The stability of an oral ready to-use form of methylergometrine (0.05 mg/mL), which provides a convenient volume for administration (5 mL), was evaluated over a forty-seven-day period at different temperatures (5 degrees C and room temperature) without light in order to assign a shelf life. Methylergometrine was assayed by a stability-indicating HPLC method with diode array detection. The drug undergoes degradation under basic conditions and dry heat (50 degrees C). All the peaks of the degraded product were resolved from the standard drug with significantly different retention times. Statistical analysis proves that the method is reproducible and accurate for estimation of the intact drug. The pH of samples was monitored periodically for changes. Samples were also visually inspected for any colour change, precipitation or crystallization. At least, 96% of the initial methylergometrine concentration remained throughout the 47-day study period. Over the test period, no significant change was observed in the pH or colour of any of the samples. No degradation products were revealed. This study allowed an oral ready to use solution of methylergometrine (0.05 mg/ml) to be prepared, with a shelf life of more than one month (47 days) when stored at room temperature without light.

Protometric thermometric titrations of sparingly soluble compounds in water in the presence of n-octanol.

Thermometric titrimetry permits titration of acido-basic compounds in water in the presence of n-octanol. n-Octanol permits the solubilization of protolytes and moreover may also displace the equilibria of the titration reactions. Hydrochlorides of highly insoluble derivatives such as phenothiazine derivatives can be titrated with satisfactory accuracy and precision by sodium hydroxide despite their high pK(a) values. Likewise barbiturate salts can be titrated by hydrochloric acid. In the case of some salts, the methodology may permit the sequential titration of the ion and counter ion.

On the reduction of dithiolethiones and dithiolylium ions by NADPH and glutathione reductase.

Results of in vitro experiments carried out in water at 25 degrees C and at pH 7.56 proved that NADPH in the presence of yeast glutathione reductase did not react with 1,2-dithiole-3-thiones and 1,2-dithiole-3-ones. On the other hand, 3-methylthiodithiolylium ions did react in these conditions. The reaction was identified and methyl 3-mercaptopropenedithioate resulting from a two-electron reduction process was obtained. A kinetic scheme consisting in a biordered mechanism has been found (Km = 2.6 10(-5) mol x l(-1)). All these results raise the question of a possible in vivo methylation (or alkylation) of dithiolethiones occurring prior to any other reductive biochemical process they may undergo. They also raise the question of the very existence (or in any case the generalization) of a reductive metabolism of dithiolethiones.

[Rigorous algorithms for calculating the exact concentrations and activity levels of all the different species during acid-base titrations in water]. / Algorithmes permettant le calcul rigoureux des concentrations et des activités des différentes espèces au cours d'un titrage acide-base en milieu aqueux.

The principles of two algorithms allowing the calculations of the concentration and activity levels of the different species during acid-base titrations in water are described. They simulate titrations at constant and variable ionic strengths respectively. They are designed so acid and base strengths, their concentrations and the titrant volume added can be chosen freely. The calculations are based on rigorous equations with a general scope. They are sufficiently compact to be processed on pocket calculators. The algorithms can easily simulate pH-metric, spectrophotometric, conductometric and calorimetric titrations, and hence allow determining concentrations and some physico-chemical constants related to the occurring chemical systems.

[Determination by thermometric titrimetry of the thermodynamic parameters of water/n-octanol transfer of several non-steroidal anti-inflammatory drugs]. / Détermination par titrimétrie thermométrique des paramètres thermodynamiques de transfert eau/n-octanol de quelques anti-inflammatoires non stéroïdiens.

The calorimetric determination by thermometric titrimetry of the water/n-octanol transfer enthalpies of some non steroidic anti-inflammatory compounds is described. By combining the values obtained with that of the free enthalpies of transfer issuing from the values of corresponding log P, it is possible to determinate the transfer entropies of the solutes. The whole results of the show that almost the transfers are both enthalpy and entropy driven. They demonstrate the occurrence of three different mechanisms of transfer.

[Chemical potentials of solutes and quantitative structure-activity relationships: study in a series of barbiturates]. / Potentiels chimiques des solutés et relations quantitatives structure-activité: étude dans la série des barbituriques.

The part, displayed by the solvatation of the solute in 2 solvents with witch log P is determined, is studied by 2 indirect process. They consist to test some QSAR where the corresponding chemical potentials are effective but with different weighs than in log P. The results obtained with barbiturics confirm the importance of the couple water/n-octanol and show that taking account of two partitionning process can improve the significativity of the QSAR.